Recent advances in basic biochemistry and exercise physiology have shown that the formation and removal of lactic acid is an integral part of both digestive and metabolic processes.
According to the `Glucose Paradox` hypothesis of McGarry (as reviewed by Foster, D., Diabetes 33:1188-1199 (1984); also see Newgard, C. B. et al., J. Biol. Chem. 258:8046-8052 (1983)), dietary carbohydrate courses an indirect route before becoming liver glycogen. It is known that dietary carbohydrate is digested and then enters the portal circulation (i.e., the vein between the small intestine and the liver) largely as glucose.
In contrast to traditional theories which hold that the liver extracts large amounts of portal blood glucose for synthesis of glycogen, it is now believed that portal glucose bypasses the liver and enters the systemic circulation through the hepatic vein. Much of this glucose then reaches the resting musculature, where it is either stored as glycogen or converted to lactic acid. This lactic acid then either diffuses or is transported from the sites of production and reaches the systemic circulation. Much of the circulating lactic acid is removed by the liver.
In the glycogen-depleted liver, lactic acid becomes the preferred precursor material from which to synthesize glycogen. Because glycogen is paradoxically synthesized by a rather circuitous pathway, the process is alternatively termed the Glucose Paradox, or the Indirect Glucose to Liver Glycogen Pathway (FIG. 1).
According to the `Lactate Shuttle` hypothesis of Brooks (Comparative Physiology and Biochemistry: Current Topics and Trends, Volume A, Respiration-Metabolism-Circulation, R. Gilles (ed.), Springer Verlag, Heidelberg, (1985); Brooks, G. A., Med. Sci. Sports Exerc. 18:360-368 (1986); Brooks, G. A., Federation Proc. 5:2924-2929 (1986); Biochemical Aspects of Physical Exercise, Brooks, G. A. et al. (eds.), Elsevier, Amsterdam, 1986); Exercise, Limits and Adaptation, Brooks, G. A. et al. (eds.), E. & F. N. Spon, London (1987)), lactic acid is an important fuel source for exercise as well as resting and exercise-recovery conditions (FIG. 2). During exercise, active fast-twitch muscles produce lactic acid, which is then available as a fuel for slow-twitch, highly oxidative skeletal muscle fibers (Donovan, C. M. and G. A. Brooks, Am. J. Physiol. 244:E83-E92 (1983); Brooks, G. A. and C. M. Donovan, Am. J. Physiol. 244:E505-512 (1983); Corsi, A. et al., Am. J. Physiol 223:219-222 (1972); Granata, A. L. et al., Pflugers Archiv. 366:247-250 (1976); Jorfeldt, L., Acta Physiol. Scand. Suppl. 338:1-67 (1971); Mazzeo, R. S. et al., Biomed. Mass. Spectrom. 9:310-314 (1982); Mazzeo, R. S. et al., J. Appl. Physiol. 60:232-241 (1986); Stanley, W. C. et al., Am. J. Physiol. 249:E595-602 (1985); Stanley, W. C. et al., J. Appl. Physiol. 60:1116-1120 (1986)) and heart tissue (Gertz, E. W. et al., Circulation .63:1273-1279 (1981)).
The oxidation of lactic acid during exercise can be appreciated on both relative and absolute bases. Of the lactic acid produced and removed during exercise, approximately 75% is removed by oxidation, and 20% is converted to glucose (Depocas, F. et al., Can. J. Physiol. Pharmacol. 47:603-610 (1969); Donovan, C. M. and G. A. Brooks, Am. J. Physiol. 244:E83-E92 (1983); Stanley, W. C. et al., Metabolism 37:850-858 (1988)). Of this latter portion, most will ultimately be oxidized also (Brooks, G. A. and C. M. Donovan, Am. J. Physiol. 244:E505-512 (1983)). Quantitatively, lactic acid oxidation exceeds glucose oxidation during exercise, with 10 to 25% of the total energy supplied derived from lactic acid oxidation. These findings suggest that it may be desirable to employ lactic acid as a supplement during and/or after exercise.
However, the use of lactic acid as a fuel in the body carries with it potential penalties. Lactic acid accumulation in the muscle is painful and interferes with contraction processes. Further, large amounts of lactic acid in the blood cause pH to fall which is physically and psychologically distressing to the performer. These disadvantages are associated with the hydrogen ion (H.sup..sym., or proton) which results when lactic acid dissociates in aqueous solutions. For these reasons, lactic acid accumulation has long been suspected as a cause of muscle fatigue (Brooks, G. A. and T. D. Fahey, Exercise Physiology: Human Bioenergetics and its Applications, Chapter 32, Macmillan, New York, 1984).
Therefore, it may be advantageous to provide glycogen depleted subjects with a `lactic acid-like` material to aid in restoration of liver glycogen as well as to restore blood glucose and muscle glycogen.
Furthermore, in comparison to providing dietary glucose to an individual engaged in prolonged, strenuous exercise, it would be more advantageous to provide a `lactic acid-like` substance which would provide a more immediate fuel source.
Thus, on the bases of both the `Glucose Paradox` and `Lactate Shuttle` concepts, providing a `lactic acid-like` material to athletes during exercise and recovery from exercise would also augment the beneficial effects of providing dietary glucose.
Disclosure of the Invention
In accordance with the present invention, a novel method and composition beneficial to a mammal's fluid, electrolyte and carbohydrate balance during exercise and subsequent recovery are provided.
In one aspect, the invention provides a method of supplying nutritional supplementation to mammals comprising providing an aqueous solution of at least one lactic acid salt. This solution is administered in oral dosage form to a mammalian host in an amount sufficient to affect the mammal's fluid, electrolyte or carbohydrate balance during exercise and/or subsequent recovery.
In another aspect, a nutritional supplement is provided comprising an aqueous solution of at least one organic lactic acid salt in an amount sufficient to affect a mammal's fluid, electrolyte or carbohydrate balance during exercise and/or subsequent recovery.
In other aspects, the present nutritional supplement includes mixtures of organic and inorganic lactic acid salts, lactate polymers, and/or simple and complex carbohydrates.